Two UK researchers who developed a mathematical model to investigate why men appear to be the weaker sex where disease is concerned suggest there may be good reasons behind the “man flu” of popular imagination: it could be the result of evolution where ability to pursue adventure and be competitive has given them greater survival advantage than building immunity to disease.

Previous studies have shown that men tend to be more exposed to infection risk than women and when they become infected their symptoms tend to be more severe and longer lasting: this has probably led to the so-called “man flu” myth.

But as Restif and Amos point out, it doesn’t make sense: why would men evolve lower immunity if they are more often exposed to infection? Surely common sense tells us that more exposure translates into more opportunity for the immune system to develop counter-measures?

So they developed a mathematical model showing why differences between male and female responses to infection may have evolved.

According to the Royal Society, this is the first such model to take an “ecological” approach to the way infectious agents or pathogens “and their hosts interact by accounting for the effect that immunity has on pathogens and vice-versa”.

The authors also point out that previous models have tended not to take into account the dynamic relationship between host and pathogens and consider this a serious omission because the level of pathogens in the environment will clearly affect the benefits of immunity.

“… a point often overlooked is that the benefits of immunity, and possibly the costs, depend not only on the host genotype but also on the presence and the phenotype of pathogens,” write the authors, who to address this issue developed an “adaptive dynamic model that includes host-pathogen population dynamics and host sexual reproduction”.

They also fed into the model various documented characteristics of males and females, including the extent of risk taking behaviour (men are more adventure seeking), and hormonal differences.

The result showed that while the more adventurous lifestyle of males means that they are more exposed to infection, it also, paradoxically, leads to them having lower immunity.

According to a report in the Telegraph, Restif told the press that:

“An increase in male susceptibility or exposure to infection favours the spread of the pathogen in the whole population and therefore tends to select for higher resistance or tolerance in both sexes if the cost of immunity is essential.”

But, and here is where the model reveals the apparent departure from common sense, “above a certain level of exposure”, said Restif, “the benefit of rapid recovery in males decreases owing to constant reinfection”.

Even men with strong immune systems that clear infection will become reinfected quickly, so the benefit of immunity is low in comparison to the cost.

“This selects for lower resistance in males, ultimately leading to the counterintuitive situation where males with higher susceptibility or exposure to infection than females evolve lower immunocompetence,” he added.

In other words, what the model appears to be saying is that in evolutionary terms, it is more important for men to maintain the ability to mate than to recover from illness, whereas in women it is the other way around.

Restif and Amos suggest that currently their model only deals with diseases that pass directly from host to host, but it could be adapted to deal with sexually transmitted diseases and “vertical transmission” from mother to offspring. This could lead to valuable insights into how viruses spread, for instance in HIV and other areas:

“We believe our framework will prove both versatile and flexible enough to be used in a range of future studies on sexual host species,” they commented.

“The evolution of sex-specific immune defences.”

Feeling better about the future might help you feel better for real. In a new study, psychological scientists Suzanne Segerstrom of the University of Kentucky and Sandra Sephton of the University of Louisville studied how law students’ expectations about the future affected their immune response. Their conclusions: Optimism may be good for your health.

Other studies have found that people who are optimistic about their health tend to do better. For example, people who are optimistic about heart transplant surgery recover better from that grueling operation. But it’s not clear how optimism affects your health -or whether pessimism makes you less healthy.

For this study, reported in Psychological Science, a journal of the Association for Psychological Science, the researchers recruited first-year law students by sending them a packet during the summer before classes started. The 124 students that participated in the research were studied at five times over six months. Each time, they answered questions about how optimistic they felt about law school. Then they were injected with material that should summon an immune response and two days later, they came back to have the injection site measured. A larger bump in the skin means a stronger immune response. Immune systems are many-faceted; this test only measures the strength of the part that is responsible for fighting viral infections and some bacterial infections.

The students’ general outlook on life – whether they had an optimistic disposition – didn’t account for the differences in immune responses between students. But as each student’s expectations about law school waxed and waned, their immune response followed along. At more optimistic times, they’d have bigger immune responses; at a more pessimistic time, a more sluggish immune response. So, being optimistic about success in a specific, important domain may promote better immunity against some infections.

Of course, the law students often have good reason to be optimistic or pessimistic; by a few months into the first semester, they’ve gotten some grades back and started to figure out if they’re good or bad at law school. “I don’t think that I would advise people that they should revise their expectations to be unrealistic,” says Segerstrom. “But if people have slightly more positive views of the future than is actually true, that’s adaptive.”

Mosquitoes transmit infectious diseases to millions of people every year, including malaria for which there is no effective vaccine. New research published in Insect Molecular Biology reveals that mosquito genetic engineering may turn the transmitter into a natural ‘flying vaccinator’, providing a new strategy for biological control over the disease.

The research, led by Associate Professor Shigeto Yoshida from the Jichi Medical University in Japan, targets the saliva gland of the Anopheles stephensi mosquitoes, the main vectors of human malaria.

“Blood-sucking arthropods including mosquitoes, sand flies and ticks transmit numerous infectious agents during blood feeding,” said Yoshida. “This includes malaria, which kills between 1-2 million people, mostly African children, a year. The lack of an effective vaccine means control of the carrier has become a crucial objective to combating the disease.”

For the past decade it has been theorized that genetic engineering of the mosquito could create a ‘flying vaccinator,’ raising hopes for their use as a new strategy for malaria control. However so far research has been limited to a study of the insect’s gut and the ‘flying vaccinator’ theory was not developed.

“Following bites, protective immune responses are induced, just like a conventional vaccination but with no pain and no cost,” said Yoshida. “What’s more continuous exposure to bites will maintain high levels of protective immunity, through natural boosting, for a life time. So the insect shifts from being a pest to being beneficial.”

In this study Dr. Yoshida’s team successfully generated a transgenic mosquito expressing the Leishmania vaccine within its saliva. Bites from the insect succeeded in raising antibodies, indicating successful immunization with the Leishmania vaccine through blood feeding.

While ‘flying vaccinator’ theory may now be scientifically possible the question of ethics hangs over the application of the research. A natural and uncontrolled method of delivering vaccines, without dealing with dosage and consent, alongside public acceptance to the release of ‘vaccinating’ mosquitoes, provide barriers to this method of disease control.

“For the past decade it has been postulated that the salivary gland could be the way to gain biological control over this important infectious disease,” concluded Yoshida. “In this study we have shown, for the first time, the achievement of the original concept of the ‘flying vaccinator.”

Millions of people in both the developing and developed world may benefit from new immune-system research findings from the University of Pennsylvania School of Veterinary Medicine.

The Penn Vet researchers, studying how the immune system operates, have discovered a previously unidentified cell population that may be the body’s double-edged sword, fighting off parasitic infections but also causing the harmful immune responses that can lead to allergies and asthma.

This cell population, termed multipotent progenitor cells, or MPP, appears to be activated in the context of allergies or infection with parasitic worms and may be one of the earliest cellular events in the developing immune response. The research published by David Artis, assistant professor in the Department of Pathobiology at Penn Vet, and colleagues may identify an important process in the immune response to helminth parasites and allergies.

A better understanding of what regulates the development of this cell population and what promotes its activation and function may aid in the development of drugs.

The research could benefit two patient populations: Those in developing countries still wrestling with parasitic worm infections and those in more industrialized environments where parasites are less prevalent but where immune responses can run amok, leading to a higher prevalence of allergies and asthma.

Millions worldwide struggle with health problems due to parasitic worms. These helminth worm parasites thrive in unsanitary conditions, in uncooked meat and in contaminated water. In more sanitary regions with fewer helminth parasites, the immune response that evolved to fight these infections may be redundant. It has been proposed that, due to reduced exposure to helminth parasites, the inactive immune response may inappropriately respond to substances like pollen, pollutants and some contents of food, resulting in exaggerated rates of asthma and allergy.

The National Institutes of Health estimates that as many as 40 to 50 million Americans suffer from allergic diseases. Consistent with this theory of redundancy, there are reports that show equatorial regions with an abundance of helminth parasites have populations that encounter lower rates of asthma and allergies.

“From an evolutionary perspective, it is likely that we evolved a complex immune response to fight parasitic worms, but our more sanitized environment no longer has this same population of parasites,” Artis said. “This newly identified cell population could represent one of the earliest events in this type of immune response, which offers potential new targets for treatment of infection and allergic inflammation.”

A research project in the Academy of Finland’s Research Programme on Nutrition, Food and Health (ELVIRA) has brought new knowledge on the hereditary nature of gluten intolerance and identified genes that carry a higher risk of developing the condition. Research has shown that the genes in question are closely linked with the human immune system and the occurrence of inflammations, rather than being connected with the actual breakdown of gluten in the digestive tract.

“Some of the genes we have identified are linked with human immune defence against viruses. This may indicate that virus infections may be connected in some way with the onset of gluten intolerance,” says Academy Research Fellow Päivi Saavalainen, who has conducted research into the hereditary risk factors for gluten intolerance.

Saavalainen explains that the genes that predispose people to gluten intolerance are very widespread in the population and, as a result, they are only a minor part of the explanation for the way in which gluten intolerance is inherited. However, the knowledge of the genes behind gluten intolerance is valuable in itself, as it helps researchers explore the reasons behind gluten intolerance, which in turn builds potential for developing new treatments and preventive methods. This is essential, because the condition is often relatively symptom-free, yet it can have serious complications unless treated.

Researchers have localised the risk genes by using data on patients and on entire families. The material in the Finnish study is part of a very extensive study of thousands of people with gluten intolerance and control groups in nine different populations. The research will be published in a coming issue of Nature Genetics.

Research into hereditary conditions has made great progress over the past few years. Gene researchers now face their next challenge, as a closer analysis is now needed of the risk factors in the genes that predispose people to gluten intolerance. It is important to discover how they impact on gene function and what part they play in the onset of gluten intolerance.

Gluten intolerance is an autoimmune reaction in the small intestine. Roughly one in a hundred Finns suffer from this condition. The gluten that occurs naturally in grains such as wheat, barley and rye causes damage to the intestinal villi, problems with nutrient absorption and potentially other problems too. Gluten intolerance is an inherited predisposition, and nearly all sufferers carry the genes that play a key part in the onset of the condition. The only known effective treatment is a lifelong gluten-free diet.

Research published in the March edition of the Journal of Thoracic Oncology (JTO) explored the importance of a patient’s outlook as it relates to health behavior and health status. Researchers focused on lung cancer patients and discovered that those who exhibited an optimistic disposition experienced more favorable outcomes than those with a pessimistic disposition.

Previous research into how the body communicates with the mind has demonstrated a connection between pessimistic outlook and negative health behaviors. The examination of a possible relationship between patient outlooks and survivorship in oncology populations is a relatively new and provocative area of investigation, and such studies have yielded mixed results. Some suggest that having a pessimistic personality before receiving a cancer diagnosis might be predictive of survival time and immune function; whereas, others have not found such an association. This newly released study builds on the existing research to gain knowledge specifically toward the effect of attitudes on lung cancer patients.

Utilizing the Optimism – Pessimism scale (PSM) of the Minnesota Multiphasic Personality Inventory (MMPI), the study investigators identified pessimistic and non-pessimistic or optimistic personality styles among patients. Researchers performed a retrospective evaluation of 534 adults diagnosed with lung cancer who had completed a MMPI about 18 years before receiving their lung cancer diagnosis between 1997 and 2006. Patients (both women and men) classified as having an optimistic attitude survived an average of six months longer compared with the patients with a pessimistic attitude. Five-year survival rates for the two groups were 32.9 percent for non-pessimists and 21.1 percent for pessimists. Furthermore, the relationship was independent of smoking status, cancer stage, treatment, comorbidities, age and gender.

Median survival:

* Overall 14.8 months

* Non-pessimistic 19.2 months

* Pessimistic 13.1 months

Five-year survival:

* Overall 27.8%

* Non-pessimistic 2.9%

* Pessimistic 21.1%

“This six-month potential benefit related to an optimistic attitude is more impressive when one considers that the median survival time for this patient population with lung cancer is less than one year,” explains the study’s lead investigator Paul Novotny, MS of the Mayo Clinic. “Despite limitations, the results may provide insights for advancing patient care in cognitive therapy, one of the many treatment dimensions. This may ultimately aid in enhancing current approaches to patient care, such that clinicians may improve survival not only by developing new medical treatments but also by targeting patient’s psychosocial characteristics most likely to negatively affect cancer treatment decisions and ultimate outcomes.”

New research has identified four aspects of immune system disturbance which lead to the development of coeliac disease. Nearly 40 different inherited risk factors which predispose to the disease have now been identified. These latest findings could speed the way towards improved diagnostics and treatments for the autoimmune complaint that affects 1 in 100 of the population, and lead to insights into related conditions such as type 1 diabetes.

David van Heel, Professor of Gastrointestinal Genetics at Barts and The London School of Medicine and Dentistry has led an international team of researchers towards the discovery. Results of their research, funded by the Wellcome Trust, and supported by the patient charity Coeliac UK, are published online in Nature Genetics on 28 Feb 2010.

Professor van Heel, commenting on the latest findings said: “We can now shed light on some of the precise immune disturbances leading to coeliac disease. These include how T cells in the body react to toxic wheat proteins, how the thymus gland eliminates these T cells during infancy, and the body’s response to viral infections. We now understand that many of these genetic risk factors work by altering the amounts of these immune system genes that cells make. The data also suggests that coeliac disease is made up of hundreds of genetic risk factors, we can have a good guess at nearly half of the genetic risk at present.”

The study also shows that there is substantial evidence to indicate a shared risk between the gene associated with coeliac disease and many other common chronic immune mediated diseases. Previously Professor van Heel had identified an overlap between coeliac disease and type 1 diabetes risk regions, as well as coeliac disease and rheumatoid arthritis.

Coeliac disease is common in the West, affecting around one per cent of the population. It is an auto-immune disease triggered by an intolerance to gluten (a protein found in foods containing wheat, barley and rye) that prevents normal absorption of nutrients. If undetected it can lead to severe health problems including anaemia, poor bone health, fatigue and weight loss.

Stress is one of the most frequently used ‘buzz words’ across Western societies with an array of meanings ranging from scientifically defined experimental conditions for laboratory animals to a casual word for a nuisance. In humans, stress is mostly used as a term for psychological hardship and it causes a variety of conditions with, psychological, medical and sociological implications.

There have been many studies on the behaviour and physiological effects of stress, but now,for the first time, Professors Hermona Soreq, Alon Friedman and Daniela Kaufer provide in their new title ‘Stress – From Molecules to Behavior’ a comprehensive overview of the molecular basis of stress from a neurolobiological and immunological perspective.

Stress – From Molecules to Behavior explores the responses and changes of the nervous system upon stress exposure, providing a unique and fundamental insight into the molecular, physiological and behavioural basis of the stress response of a whole organism.

“It is well known that stress response may induce profound behavioural changes as well as physiological changes in the nervous and the immune system,” said Editor Professor Hermona Soreq from the Hebrew University of Jerusalem. “Unfavourable consequences of stress response are a common health problem in many societies, but studying the underlying molecular mechanisms driving stress induced changes opens the possibility of more targeted therapeutic approaches.”

Stress – From Molecules to Behavior takes a strong interdisciplinary approach, dealing with stress from a neurological, medical, behavioural, immunological and cellular angle. This approach provides an insight into the molecular alterations of the nervous system in response to stress, the molecular basis of stress related cognition and behavioural changes, and explores the interplay between the nervous and the immune system upon stress exposure.

Key sections of the title deal with neurotransmitter release, hormone metabolism and neurogenesis in response to stress stimuli, as well as the consequences of these factors on the immune system and the consequential behaviour of individuals.

Retroviruses such as HIV and HTLV-1 don’t hit-and-run, they hit-and-hide. They slip into host cells and insert their own DNA into the cell’s DNA, and from this refuge they establish an infection that lasts a lifetime.

But that infection might be much less troublesome and much more manageable if the immune system could mount a strong response to the virus during its first few days in the body, according to a new study by cancer researchers at the Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC-James).

The animal study, published online in the journal Blood, examined the human T-lymphotropic virus type 1 (HTLV-1), which causes adult T-cell leukemia and several inflammatory diseases in some people.

“Our findings indicate that if the immune system could respond strongly to HTLV-1 and kill infected target cells early, it may inhibit the virus’s ability to establish reservoirs of infected cells and make the infection more manageable later,” says principal investigator Michael Lairmore, a professor and chair of veterinary biosciences and a cancer researcher at OSUCCC-James.

“This study tells us that the more we know about the earliest events of infection, the more it will help us develop vaccines and might block those events.”

Lairmore and his colleagues examined HTLV-I infection in rabbits that were treated with the drug cyclosporin A, which is commonly used to suppress the immune system in people following organ transplantation. The researchers compared animals treated with this drug prior to viral infection with those given the drug one week after infection.

This study builds on earlier work by Lairmore and his colleagues showing that HTLV-I produces proteins that activate infected immune cells and causes them to divide, thereby increasing the number of infected cells in the body. The researchers found that cyclosporin A blocked that activation.

In this new study, the researchers used cyclosporin A to learn whether modifying the immune response – by providing fewer immune cells for the virus to attack – at a critical time, after the first week of infection when the virus needs to spread, would influence the extent of the infection weeks later.

In animals given the immune-suppressing drug first, the virus flourished. The number of virus copies jumped to 200 per 10,000 immune cells (lymphocytes), compared with 40 per 10,000 immune cells in control animals (these were infected with the virus but not given the drug). After a week or two, the number of virus copies fell, ranging from 113 to 160 for remainder of the 10-week experiment.

In the animals that were given the virus first and then the immune-suppressing drug a week later, on the other hand, the virus languished. The number of virus copies in these animals was lower than the controls, and it remained that way throughout the 10-week experiment. At week four after infection, for example, the immune-suppressed animals had on average nine virus copies per 10,000 immune cells, compared with 40 copies in control samples. At week 10, they had 10 virus copies compared with 30 in controls.

“The first experiment told us that if the immune system is suppressed, the viral load goes up – and we expected that,” says Lairmore. “The second group was the surprise. Their viral load was low from the start, and it stayed that way. We didn’t expect that. We thought the virus would recover and come back up.

“Collectively, our findings indicate that the immune system plays a key role in controlling HTLV-1 spread during early infection, which has important implications for a vaccine against this virus and for therapy for HTLV-1-associated diseases,” says Lairmore.

Two new studies showing that protein bits produced by unusual “reading” of the HIV genome can induce immune responses appeared online in the Journal of Experimental Medicine on Jan. 11.

Small, compact RNA viruses like HIV make the most of their limited genomes by stuffing genes that direct protein production into several different reading frames and orientations. When teams – led by Berger et al. at the Ragon Institute of MGH, MIT, and Harvard; and Bansal et al. at the University of Alabama – examined viral genomes in groups of HIV-infected individuals, they found an accumulation of genetic variations specifically in unusual reading frames and orientations. This finding suggested that mutations in these reading frames may have been caused by pressure from the hosts’ immune systems.

The notion was supported by their finding that HIV-infected individuals exhibited killer immune cell responses specific for protein fragments generated by unconventional reading of the HIV genome. In some cases, mutations in these reading frames allowed HIV-infected cells to escape immune cell killing.

The information provided by these findings may prove useful during future HIV vaccine design efforts.